Submissions for variant NM_001271.4(CHD2):c.5134C>T (p.His1712Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1006465697

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001946251	SCV002213602	uncertain significance	Developmental and epileptic encephalopathy 94	2020-12-19	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHD2 protein function. This variant has not been reported in the literature in individuals with CHD2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 1712 of the CHD2 protein (p.His1712Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine.
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV003126010	SCV003803767	likely benign	Autism spectrum disorder	2022-07-28	criteria provided, single submitter	clinical testing